Dual-action depot formulation of hyaluronic acid/poloxamer in-situ gel enclosing lavender oil-based syringic acid nanoemulsion for enhanced intra-articular treatment of osteoarthritis

Osteoarthritis (OA) is a degenerative disorder affecting the joints and is portrayed by chronic pain and inflammation, impacting quality of life. Conventional treatments show limited efficacy due to inadequate drug delivery and suboptimal retention. The unique anti-inflammatory effects of syringic acid (SA) can be potentiated with the incorporation of lavender oil in a nanoemulsion for intra-articular delivery.
Integrating a novel hyaluronic acid/poloxamer 407/poloxamer 188 (HA/P407/P188) in situ gel with SA-loaded lavender oil-based nanoemulsion was attempted. Colloidal features and suitability of the corresponding in situ gel for intra-articular delivery were demonstrated. In-vivo therapeutic efficacy on knee osteoarthritis induction model was also investigated.
The proposed nanoemulsion was designed with a droplet size of 214.5 ± 19.54 nm and a polydispersity index of 0.387 ± 0.060. HA/P407/P188 in situ gel further augments therapeutic outcomes for intra-articular administration by prolonging SA release approaching 6 days and offering appropriate sol–gel transition temperature and rheological patterns. In-vivo anti-arthritic activity was confirmed with a more reduced joint inflammation and downregulation of pro-inflammatory cytokine levels in knee joints compared to SA suspension.
This study highlights the potential of the nanoemulsion in a HA/P407/P188 in-situ gel as a promising strategy for intra-articular OA therapy, with an enhanced sustained therapeutic efficacy.
An effective liquid/gel delivery system as an anti-inflammatory medicine for osteoarthritis treatment
Arthritis in knee joints is a disease that causes chronic pain and inflammation in joints, leading to reduced quality of life. Current treatments depend on oral medications that decrease inflammation but they do not deliver drugs to the joints. Besides, they cause unwanted side effects. In this study, we made a new liquid for direct administration into joints using nanosized emulsion containing two natural therapeutic agents: syringic acid and lavender oil that have anti-inflammatory properties. To help prolong presence at the joint, the nanosized emulsion was incorporated in a liquid form made of hyaluronic acid and poloxamer polymers that can turn into gel when heated at body temperature. This was called in situ gel. We found that it helped the incorporated therapeutic agents work better and prolong syringic acid release. Our tests in rats showed that it can significantly reduce the inflammation of the joint compared to drug suspension. This new medicine may be better effective platform than oral therapies for treatment of arthritis.